Cedars-Sinai Study: How Does a "Good" Protein Hurt Brain Cells After Clot-Induced Stroke

$1.4 million NIH grant will support Department of Neurology research

Los Angeles - Nov. 22, 2011 – The National Institutes of Health has awarded a four-year, $1.4 million grant to Cedars-Sinai’s Department of Neurology to study an unexpected recent discovery: After ischemic stroke – the type caused by a clogged artery but with no bleeding into the brain – a normal protein that plays a positive role in blood clotting escapes intact arteries and damages healthy brain cells.

“We knew thrombin leaked out during hemorrhagic strokes – those in which an artery ruptures – and we knew that in large amounts it killed brain cells. But we decided to see if there was thrombin after ischemic stroke, and, surprisingly, there was a lot, and it was causing major damage to brain cells. When we injected a drug that counters the effects of thrombin, stroke symptoms got better,” said Patrick D. Lyden, MD, chair of the Department of Neurology and the Carmen and Louis Warschaw Chair in Neurology at Cedars-Sinai.

He was senior author of a 2010 article in the journal Stroke that described this phenomenon and suggested possible underlying mechanisms. The new grant, he said, will let researchers delve more deeply: Where is the thrombin coming from? What kinds of cells does it kill? What factors inhibit or enhance its effects?

Lyden will continue his work with Roger Y. Tsien, a scientist at the University of California, San Diego. He is one of three winners of the 2008 Nobel Prize in chemistry for development of green fluorescent protein.

Lyden’s study will use fluorescence in rats and mice to light up thrombin and follow its migration and interactions with other molecules in blood vessels and brain tissue.

This is the first NIH funding directly awarded to the Department of Neurology, evidence of its growth since Lyden’s arrival in 2009. He and other researchers are also supported by other NIH grants received before he joined Cedars-Sinai.

Lyden is principal investigator of the “ICTuS” (Intravascular Cooling in the Treatment of Stroke) trials evaluating post-stroke hypothermia therapy in a variety of patient populations and circumstances. The rapid, controlled cooling of a patient’s body temperature is intended to reduce long-term neurological damage. He also was one of the key researchers in the major clinical trial leading to Food and Drug Administration approval in 1996 of tPA – tissue plasminogen activator – which remains the only proven and approved drug for stroke treatment.